MER Proto-Oncogene Tyrosine Kinase: A Novel Potential Target to Treat Nonalcoholic Steatohepatitis Fibrosis.

Abstract

A recent elegant study by Cai et al. (1) entitled "Macrophage MerTK Promotes Liver Fibrosis in Nonalcoholic Steatohepatitis" uncovered a novel potential therapeutic target to treat nonalcoholic steatohepatitis (NASH) fibrosis. It is reported that the rs4374383 G>A variant of the MerTK gene is associated with reduced MerTK mRNA expression in livers (2). Importantly, NASH patients carrying this variant appear to be more resistant to developing fibrosis compared with those harboring the major G allele (2). However, the underlying mechanisms are unknown. Cai et al. reported that the MerTK signaling in hepatic macrophages resulted in TGFβ1 production and hepatic stellate cell (HSC) activation, thereby promoting disease progression from steatosis to NASH fibrosis. Interestingly, the data suggest that all-trans retinoic acid (ATRA)-induced ADAM17-mediated MerTK cleavage plays a critical role in regulating the levels of MerTK receptor on macrophages and that this pathway is impaired in NASH fibrosis. .